9-137710882-T-C

Position:

• chr9-137710882-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024757.5(EHMT1):​c.22-85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,475,878 control chromosomes in the GnomAD database, including 129,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13304 hom., cov: 32)
  • Exomes 𝑓: 0.41 (116673 hom.)
• Consequence: EHMT1 NM_024757.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07

Genes affected

EHMT1 (HGNC:24650): (euchromatic histone lysine methyltransferase 1) The protein encoded by this gene is a histone methyltransferase that methylates the lysine-9 position of histone H3. This action marks the genomic region packaged with these methylated histones for transcriptional repression. This protein may be involved in the silencing of MYC- and E2F-responsive genes and therefore could play a role in the G0/G1 cell cycle transition. Defects in this gene are a cause of chromosome 9q subtelomeric deletion syndrome (9q-syndrome, also known as Kleefstra syndrome). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-137710882-T-C is Benign according to our data. Variant chr9-137710882-T-C is described in ClinVar as [Benign]. Clinvar id is 1292360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHMT1	NM_024757.5	c.22-85T>C		intron_variant		ENST00000460843.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHMT1	ENST00000460843.6	c.22-85T>C		intron_variant		5	NM_024757.5

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61777 AN: 151842 Hom.: 13293 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.407 AC: 539428 AN: 1323920 Hom.: 116673 AF XY: 0.414 AC XY: 270639 AN XY: 653778

Gnomad4 AFR exome AF: 0.433

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.830

Gnomad4 SAS exome AF: 0.620

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.407 AC: 61827 AN: 151958 Hom.: 13304 Cov.: 32 AF XY: 0.411 AC XY: 30526 AN XY: 74274

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.403

Alfa AF: 0.378 Hom.: 14502

Bravo AF: 0.404

Asia WGS AF: 0.723 AC: 2513 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7039441; hg19: chr9-140605334;